Quench liquids and washing systems for production of microparticles

Abstract

The present invention provides coacervation methods forming compositions for the sustained release water soluble active agents, including biologically active polypeptides. The invention further relates to the discovery of improved non-aqueous quench liquids and washing systems, which enable a reduction in the amount and concentration of hardening agents such as heptane used to produce microparticles, while providing acceptable product yields and residual solvent levels.

Description

RELATED APPLICATION[0001]This application claims the benefit of U.S. Provisional Application No. 60 / 945,188, filed on Jun. 20, 2007. The entire teaching of the above application is incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Numerous proteins and peptides, collectively referred to herein as polypeptides, exhibit biological activity in vivo and are useful as medicaments. Many illnesses or conditions require maintenance of a sustained level of medicament to provide the most effective prophylactic and / or therapeutic effects. Sustained levels are often achieved by the administration of biologically active polypeptides by frequent subcutaneous injections, which often results in fluctuating levels of medicament and poor patient compliance.[0003]As an alternative, the use of biodegradable materials, such as polymers, encapsulating the medicament can be employed as a sustained delivery system. The use of biodegradable polymers, for example, in the form of microparticle...

AI Technical Summary

Benefits of technology

[0018]This invention relates to coacervation processes for forming compositions for the sustained release of water soluble active agents, including biologically active polypeptides. The invention further relates to the discovery of improved n

Problems solved by technology

Sustained levels are often achieved by the administration of biologically active polypeptides by frequent subcutaneous injections, which often results in fluctuating levels of medicament and poor patient compliance.

On the other hand, water soluble drugs may partially partition into the aqueous phase during the preparation process, resulting in a low encapsulation efficiency.

However, the removal of residual solvents, including halogenated solvents commonly used to dissolve the polymer, from microparticles formed by coacervation can be inefficient.

Efforts to lower residual solvent levels can result in lower microparticle yields due to additional processing, or lower potency due to partial extraction of the active agent during solvent removal.

In addition, coacervation processes known in the art consume large volumes of organic solvents when carried out at a commercial scale.

A major contributor to solvent consumption is the quench step, which typically employs heptane as a hardening solvent.

Moreover, the quantity of microparticles that can be produced in a single batch is often limited by the capacity of the quench tank.

Furthermore, pure heptane does not dissipate static charge well, which may present a fir

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